Documents\Palladium-contents. Pdf

Summary
9
reactivity  to  nickel  sulfate  in  animals   sensitized  with  palladium(II)
chloride  could   be  attributed  to  cross-reactivity.  Respiratory
sensitization (bronchospasms) has  been observed in cats after intra-
venous administration of several complex palladium compounds. It was
accompanied by an increase in serum histamine. Significant immune
responses   have  been  obtained  with  palladium(II)  chloride  and/or
chloropalladates  using the popliteal and auricular lymph node assay in
BALB/c mice. Preliminary data in an animal model suggest that palla-
dium(II) compounds may be involved in induction of an autoimmune
disease.
There  are  insufficient data on the reproductive and developmental
effects   of  palladium  and  its   compounds. In one screening study,
reduced testis  weights  were  reported in mice that had received 30 daily
subcutaneous doses of palladium(II) chloride  at  a  total  d o s e  of
3.5 mg/kg body weight.
Palladium compounds may interact with isolated DNA  in vitro .
However, with one exception, mutagenicity tests of several palladium
compounds with bacterial or mammalian cells  in  vitro   (Ames   test:
Salmonella typhimurium; SOS chromotest: Escherichia coli; micro-
nucleus test: human lymphocytes) gave negative results. Also, an in
vivo genotoxicity test (micronucleus t e s t in mouse) with tetraammine
palladium hydrogen carbonate gave negative results.
Tumours  associated with palladium exposure have been reported
in two  studies. Mice given palladium(II) chloride (5 mg Pd
2+
/litre) in
drinking-water from weaning until natural death developed malignant
tumours, mainly  lymphoma–leukaemia  types and adenocarcinoma  of
the lung, at a statistically  significant rate, but concomitant with an
increased longevity in males, which may explain at least in part the
increased tumour rate. Tumours were found at the implantation site in
7 of 14 rats (it was not clear whether the tumours were due to the
chronic  physical stimulus or to the chemical components) 504 days
after subcutaneous implantation of a silver–palladium–gold alloy. No
carcinogenicity study with inhalation exposure was available.
Palladium  ions  are   capable   of  inhibiting  most  major cellular
functions, as  seen in vivo and in vitro . DNA/RNA  biosynthesis  seems
to be the most sensitive target. An EC
50
 value of palladium(II) chloride
for inhibition of DNA synthesis in vitro  with mouse fibroblasts  was

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EHC 226: Palladium
10
300 µmol/litre (32 mg Pd
2+
/litre). Inhibition of DNA  synthesis  in vivo (in
spleen, liver, kidney and testes) occurred in rats administered a single
intraperitoneal d o s e of 14 µmol palladium(II) nitrate (Pd(NO
3
)
2
)/kg  body
weight (1.5 mg Pd
2+
/kg body weight).
Palladium applied in its  metallic form showed no or little in vitro
cytotoxicity, as evaluated microscopically.
A  series  of isolated enzymes  having key metabolic  functions have
been found to be inhibited by simple  and complex palladium salts. The
strongest inhibition (K
i
 value for palladium(II) chloride
 
= 0.16 µmol/litre)
was   found  for  creatine  kinase,  an  important  enzyme of energy
metabolism. 
Many  palladium–organic   complexes   have an antineoplastic
potential similar to that of cis-dichloro-2,6-diaminopyridine-platinum(II)
(cis-platinum, an anticancer drug).
The mode of action of palladium ions and of elemental palladium
is  not fully clear. Complex formation of palladium ions with cellular
components probably plays a basic role initially. Oxidation processes
may also be involved, due to the different oxidation states  of palladium.
1.7
Effects on humans 
There is no information on the effects  of palladium emitted from
automobile  catalytic  converters  on the general population. Effects  have
been reported due to iatrogenic and other exposures.
Most of the case reports  refer to palladium sensitivity associated
with exposure to palladium-containing dental restorations, symptoms
being contact dermatitis, stomatitis  or mucositis  and oral lichen planus.
Patients  with positive palladium(II) chloride patch tests did not neces-
sarily  react to metallic palla dium. Only a few persons who showed
positive patch test results with palladium(II) chloride showed clinical
symptoms in the oral mucosa as a result of exposure to palladium-
containing alloys. In one study, slight but non-significant changes in
serum immunoglobulins were  seen after placement of a silver–palla-
dium alloy dental restoration.

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Summary
11
Side-effects   noted  from  other  medical  or  experimental uses of
palladium  preparations  include  fever,  haemolysis,  discoloration  or
necrosis  at injection sites  after subcutaneous injections and erythema
and oedema following topical application.
A few case reports  reported skin  disorders  in patients  who had
exposure to palladium-containing jewellery or unspecified sources.
Serial  patch  tests   with  palladium(II) chloride  indicated  a  high
frequency  of  palladium  sensitivity in special groups under study.
Several recent and large-sized studies  from different countries found
frequencies  of palladium sensitivity of 7–8%  in patients  of dermatology
clinics  as  well as in schoolchildren, with a preponderance in females
and younger persons. Compared with other allergens (about 25 were
studied), palladium belongs to the seven most frequently  reacting sen-
sitizers (ranked second after nickel within  metals). Solitary palladium
reactions (monoallergy) occurred with a low frequency. Mostly, com-
bined reactions with other metals  (multisensitivity), primarily nickel,
have been observed.
To date, the most often identified sources  of palla d i u m   s e n s i -
tization for the general population are  dental restorations and jewellery.
There are few data on adverse health effects due to occupational
exposure  to palladium. Few PGM  workers  (2/307; 3/22) showed positive
reactions to a complex palladium halide salt  in sensitization tests (skin
prick  test;  radioallergosorbent test; monkey passive cutaneous
anaphylaxis  test). Some  workers  (4/130) of an automobile  catalyst plant
had  positive  reactions  in  prick  tests  with palladium(II) chloride.   A
review article  (without details) reported on a frequent occurrence of
allergic   diseases   of  the  respiratory   passages,  dermatoses   and
affections of the eyes  among Russian PGM  production workers. Single
cases  of allergic contact dermatitis have been documented for two
chemists and a metal worker. A  single case of palladium salt-induced
occupational asthma has been observed in the electronics industry.
Subpopulations at special risk of palladium allergy include people
with known nickel allergy.

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